RECOMBINANT LEECH ANTIPLATELET PROTEIN PREVENTS COLLAGEN-MEDIATED PLATELET-AGGREGATION BUT NOT COLLAGEN GRAFT THROMBOSIS IN BABOONS

Leech antiplatelet protein (LAPP) is a specific inhibitor of collagen- induced human platelet aggregation and adhesion to collagen under stat ic conditions. Recombinant LAPP (rLAPP) and L-366,763 (acetylated-Cys- Asn-Pro-Arg-Gly-Asp-Cys-NH2), a peptidyl fibrinogen receptor antagonis t, were evaluated in an anesthetized baboon thrombosis model using a c ollagen-coated graft segment of an arteriovenous shunt to elicit throm bus formation. Animals were randomized to receive systemic intravenous administration of rLAPP (100 mug . kg-1 . min-1; n=5), L-366,763 (8.5 mug . kg-1 . min-1; n=3), or saline (n=3). Despite complete and selec tive inhibition of type I collagen-induced ex vivo aggregation of plat elets, rLAPP had no significant effect on the rate or the extent of In -111-labeled platelet deposition onto the collagen graft and no effect on template bleeding time. In contrast, L-366,763 completely prevente d platelet deposition, maintained blood flow, and significantly prolon ged bleeding time at the dosage that inhibited ex vivo aggregation in response to all agonists studied. In this study, the absence of an ant ithrombotic benefit of rLAPP contrasted sharply with the efficacy of t he fibrinogen receptor antagonist. These results demonstrate that spec ific inhibition of collagen-mediated platelet aggregation alone is not sufficient to prevent platelet-dependent thrombosis in this baboon mo del.